Evaluation of potential metabolomic-based biomarkers of protein, carbohydrate and fat intakes using a controlled feeding study

Cheng Zheng, G. A.Nagana Gowda, Daniel Raftery, Marian L. Neuhouser, Lesley F. Tinker, Ross L. Prentice, Shirley A.A. Beresford, Yiwen Zhang, Lisa Bettcher, Robert Pepin, Danijel Djukovic, Haiwei Gu, Gregory A. Barding, Xiaoling Song, Johanna W. Lampe

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Purpose: Objective biomarkers of dietary exposure are needed to establish reliable diet-disease associations. Unfortunately, robust biomarkers of macronutrient intakes are scarce. We aimed to assess the utility of serum, 24-h urine and spot urine high-dimensional metabolites for the development of biomarkers of daily intake of total energy, protein, carbohydrate and fat, and the percent of energy from these macronutrients (%E). Methods: A 2-week controlled feeding study mimicking the participants’ habitual diets was conducted among 153 postmenopausal women from the Women’s Health Initiative (WHI). Fasting serum metabolomic profiles were analyzed using a targeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for aqueous metabolites and a direct-injection-based quantitative lipidomics platform. Urinary metabolites were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy at 800 MHz and by untargeted gas chromatography–mass spectrometry (GC–MS). Variable selection was performed to build prediction models for each dietary variable. Results: The highest cross-validated multiple correlation coefficients (CV-R2) for protein intake (%E) and carbohydrate intake (%E) using metabolites only were 36.3 and 37.1%, respectively. With the addition of established dietary biomarkers (doubly labeled water for energy and urinary nitrogen for protein), the CV-R2 reached 55.5% for energy (kcal/d), 52.0 and 45.0% for protein (g/d, %E), 55.9 and 37.0% for carbohydrate (g/d, %E). Conclusion: Selected panels of serum and urine metabolites, without the inclusion of doubly labeled water and urinary nitrogen biomarkers, give a reliable and robust prediction of daily intake of energy from protein and carbohydrate.

Original languageEnglish (US)
Pages (from-to)4207-4218
Number of pages12
JournalEuropean Journal of Nutrition
Issue number8
StatePublished - Dec 2021


  • Carbohydrate
  • Controlled feeding study
  • Dietary biomarker
  • Metabolomics
  • Postmenopausal women
  • Protein

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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